Neuromuscular blocking agents (NMBAs) are widely administered during anethesia to prevent the patient from moving and optimize surgical conditions. Timely reversal of the muscle relaxation state induced by NMBAs at the end of surgery is necessary to recover autonomous respiration and muscle function. Herein, an extended biphen[3]arene carboxylate (ExBP3C) was designed and synthesized by a supramolecular sequestration approach as a reversal agent with high efficiency and generality against several representative NMBAs. ExBP3C exhibited robust host-guest complexation toward atracurium, rocuronium, vecuronium, pancuronium, and gallamine with an association constant of up to 108 M-1. A series of in vitro and in vivo safety tests preliminarily demonstrated that this synthetic macrocycle had good biocompatibility. Compared to sugammadex, post-treatment by an equivalent dose of ExBP3C could produce a more efficient reversal function. Additionally, a single dose of such a reversal agent was also able to completely recover overdose atracurium-induced heart rate abnormalities within 2 min.